Dietary fructose exacerbates hepatocellular injury when incorporated into a methionine-choline-deficient diet
Version of Record online: 8 JUN 2010
© 2010 John Wiley & Sons A/S
Volume 30, Issue 8, pages 1229–1239, September 2010
How to Cite
Pickens, M. K., Ogata, H., Soon, R. K., Grenert, J. P. and Maher, J. J. (2010), Dietary fructose exacerbates hepatocellular injury when incorporated into a methionine-choline-deficient diet. Liver International, 30: 1229–1239. doi: 10.1111/j.1478-3231.2010.02285.x
- Issue online: 3 AUG 2010
- Version of Record online: 8 JUN 2010
- Received 21 July 2009Accepted 1 May 2010
- de novo lipogenesis;
- fatty acid;
- fatty liver;
Background: Methionine-choline-deficient (MCD) diets cause steatohepatitis in rodents and are used to model fatty liver disease in human beings. Recent studies have identified sucrose as a major contributor to MCD-related liver disease through its ability to promote hepatic de novo lipogenesis.
Aims: To determine whether glucose and fructose, the two constitutents of sucrose, differ in their capacity to provoke steatohepatitis when incorporated individually into MCD formulas.
Materials & Methods: MCD and control formulas prepared with either glucose or fructose as the sole source of carbohydrate were fed to mice for 21 days. Liver injury was assessed biochemically and histologically together with hepatic gene expression and fatty acid analysis.
Results: Mice fed MCD formulas developed similar degrees of hepatic steatosis whether they contained glucose or fructose. By contrast, mice fed MCD-fructose developed significantly more hepatocellular injury than mice fed MCD-glucose, judged by histology, apoptosis staining and serum alanine aminotransferase. Liver injury in MCD-fructose mice coincided with an exaggerated rise in the ratio of long-chain saturated to unsaturated fatty acids in the liver. Notably, hepatic inflammation was not enhanced in mice fed MCD-fructose, correlating instead with hepatic lipid peroxidation, which was equivalent in the two MCD groups.
Discussion: Fructose is more cytotoxic than glucose when used as the source of carbohydrate in MCD formulas.
Conclusion: The data suggest the enhanced cytotoxicity of fructose in the MCD model is related to its ability to stimulate de novo lipogenesis, which yields harmful long-chain saturated fatty acids.